Bone aluminum accumulation in the current era / Acúmulo de alumínio no tecido ósseo na era atual

In the last few years, evidence from the Brazilian Registry of Bone Biopsy (REBRABO) has pointed out a high incidence of aluminum (Al) accumulation in the bones of patients with CKD under dialysis. This surprising finding does not appear to be merely a passive metal accumulation, as prospective data from REBRABO suggest that the presence of Al in bone may be independently associated with major adverse cardiovascular events. This information contrasts with the perception of epidemiologic control of this condition around the world. In this opinion paper, we discussed why the diagnosis of Al accumulation in bone is not reported in other parts of the world. We also discuss a range of possibilities to understand why bone Al accumulation still occurs, not as a classical syndrome with systemic signs of intoxication, as occurred it has in the past.

Nos últimos anos, evidências do Registro Brasileiro de Biópsia óssea (REBRABO) apontaram uma alta incidência de intoxicação por alumínio (Al) no tecido ósseo de pacientes com DRC em diálise. Essa surpreendente informação parece representar não apenas um acúmulo passivo deste metal, visto que dados prospectivos do REBRABO sugerem que a presença de Al no tecido ósseo pode estar independentemente relacionada a eventos cardiovasculares adversos maiores. Essas informações contrastam com a percepção mundial do controle epidemiológico dessa condição. Neste artigo de opinião, discutimos por que o diagnóstico de acúmulo ósseo de Al não é relatado em outras partes do mundo, e também discutimos uma gama de possibilidades para entender por que nós acreditamos que o acúmulo de Al no tecido ósseo ainda ocorre, não como se apresentava no passado, ou seja, como uma síndrome com sinais e sintomas sistêmicos de intoxicação.

Sub-chronic aluminum exposure induces cognitive impairment through ALKBH5/PTEN/AKT signaling pathway in rats / 中国职业医学

ObjectiveTo investigate the effects of maltol aluminum exposure on miR-193a-3p, demethylase AlkB homolog 5 (ALKBH5), phosphatase and tensin homolog deleted on chromosome ten (PTEN) and protein kinase B (AKT), and whether miR-193a-3p is involved in aluminum-induced cognitive impairment by regulating ALKBH5/PTEN/AKT signaling pathway. Methods Specific pathogen-free male SD rats were randomly divided into control group and low-, medium- and high- dose groups according to their body weight, with eight rats in each group. Rats in the low-, medium-, and high- dose groups were intraperitoneally injected with maltol aluminum solution at concentrations of 10.00, 20.00, and 40.00 μmol/kg body weight, respectively, while the rats in control group were given an equal volume of 0.9% sodium chloride solution. Rats were injected for five days every week for three months. After injection, the novel object recognized test was used to assess the learning and memory ability of the rats. The relative expression of miR-193a-3p and B-cell lymphocytoma-2 (Bcl-2), Bcl-2 associated X protein (Bax) and cysteine aspartate protease-3 (Caspase-3) mRNA in rat hippocampus was detected using the real-time quantitative polymerase chain reaction. The relative protein expression of ALKBH5, PTEN, and AKT2 in the rat hippocampus was detected using Western blot. Results The discrimination index and the preference index of the new object recognition test of the rats in high-dose group were lower than those in control group and low-dose group (all P<0.05). The relative expression of miR-193a-3p and Bcl-2 mRNA in the hippocampus of the rats in high-dose group was lower than those in control group and low-dose group (all P<0.05). The relative mRNA expression of Bax in the high-dose group was higher than those in the control group and low-dose group (both P<0.05). The relative mRNA expression of Caspase-3 of the rats in the high-dose group was higher than that in the other three groups (both P<0.05). The relative protein expression of ALKBH5 in the hippocampus of the rats in the high-dose group was lower than that in the control group (P<0.05). The relative expression of PTEN protein was higher than those in the control group and low-dose group (both P<0.05). The relative protein expression of AKT2 was lower than those in the control group and low-dose group (both P<0.05). Conclusion Sub-chronic aluminum exposure can inhibit the expression of miR-193a-3p in the hippocampus of rats, which may disrupt the ALKBH5/PTEN/AKT pathway and affect normal neuronal homeostasis and cellular function. This pathway may play an important role in aluminum-induced cognitive impairment.

Cu0 Modification and Cu2+ Self-intercalation of Ti3C2Tx Two-dimensional Material for Electrocatalytic Reduction of CO2 / 分析化学

The conversion of carbon dioxide into high value-added energy has become a research hotspot.In this study,by using Ti3AlC2 and CuCl2·2H2O as precursors,accordion-like two-dimensional Cu0/Cu2+-Ti3C2Tx catalysts modified with Cu0 nanoparticles and Cu2+ self-intercalation were successfully prepared for electrocatalytic reduction of CO2.The performance of the material was tested,and the results showed that in a CO2-saturated 0.5 mol/L KHCO3 electrolyte solution,compared with the original Ti3AlC2,the initial potential of the electrocatalytic conversion of CO2 to C2H4 over Cu0/Cu2+-Ti3C2Tx catalyst decreased from ?0.65 V(vs RHE)to?0.01 V(vs RHE).The maximum current density increased from 0.19 mA/cm2 to 2.5 mA/cm2,the double layer capacitance(Cdl)value increased from 2.61 mF/cm2 to 55.06 mF/cm2.The material showed higher catalytic activity and faster electron transfer rate(Charge transfer resistance(Rct)value was only 16.9 Ω).Moreover,the material showed high electrochemical active area and excellent stability.This research provided a promising method for designing and preparing elcetrocatalytic reduction(ECR)catalysts in the future.

Effect of neodymium-doped:yttrium aluminum perovskite laser combined with two kinds of remineralizers on remineralization of early enamel caries / 中国组织工程研究

BACKGROUND:In recent years,a variety of lasers have been widely used in various diseases related to stomatology,including the prevention and treatment of dental caries. OBJECTIVE:To investigate the effect of neodymium-doped:yttrium aluminum perovskite(Nd:YAP)laser combined with two remineralizers on early enamel caries in vitro. METHODS:Early enamel caries models in vitro were artificially established by 60 enamel blocks and randomly divided into 6 groups(n=10).Group A did not undergo any treatment but underwent extracorporeal pH circulation.Group B underwent remineralization of dentin(the main component of casein phosphopeptide-amorphous calcium phosphate composite)and extracorporeal pH circulation.Group C underwent remineralization treatment of Sensodyne toothpaste(the main component of bioactive glass)and then underwent extracorporeal pH circulation.Group D received Nd:YAP laser irradiation and extracorporeal pH circulation.Group E was treated with Nd:YAP laser irradiation,with remineralization of dentin,and then with extracorporeal pH circulation.In group F,Nd:YAP laser irradiation was performed,and then Sensodyne toothpaste was used for remineralization,and the extracorporeal pH circulation was performed;the remineralization treatment was conducted twice a day,and the experimental period was 20 days.Group G was a normal control group,without caries or remineralization,but only underwent extracorporeal pH circulation.After the experiment,the microhardness,morphology and Ca/P ratio of the dental enamel surface were measured in each group. RESULTS AND CONCLUSION:(1)The surface microhardness value of dental enamel in groups B,C and D was higher than that in group A(P<0.000 1);the surface microhardness value of dental enamel in groups E and F was significantly higher than that in groups B,C and D(P<0.000 1),and the surface microhardness value of dental enamel in group F was significantly higher than that in group E(P<0.000 1).(2)Scanning electron microscopy showed that there were a lot of demineralized pores on the enamel surface of group A.There were mineral deposits on the enamel surface of group B,which were uneven and loose.In group C,there were a lot of mineral deposits on the enamel surface,and demineralized pores were found between the calcified masses.The enamel surface of group D was relatively flat;the demineralized pores were significantly smaller than that of group A,and the enamel column interstitium was damaged.In group E,the mineral deposits on the enamel surface were thicker and the demineralized pores were significantly reduced.The mineralized substances deposited on the enamel surface of group F were most dense and uniform and the demineralized pores were small.(3)The Ca/P ratio on the enamel surface of groups B and C was significantly higher than that of group A(P<0.000 1);the Ca/P ratio on the enamel surface of group E was significantly higher than that of groups B,C and D(P<0.000 1),and the Ca/P ratio on the enamel surface of group F was higher than that of group E(P<0.001).(4)These findings indicate that bioactive glass,casein phosphopeptide-amorphous calcium phosphate composite,and Nd:YAP laser after enamel demineralization can promote the remineralization of early enamel caries.Nd:YAP laser combined with bioactive glass or casein phosphopeptide-amorphous calcium phosphate composite can further strengthen the remineralization of dental enamel caries,and the combination of Nd:YAP laser and bioactive glass has the best effect.

The complication rate following Neodymium-doped Yttrium Aluminum Garnet laser posterior capsulotomy for posterior capsular opacification in patients with and without comorbidities

Purpose: To study the complication rate following Nd: YAG posterior capsulotomy posterior capsular opacification (PCO) in patients with and without comorbid conditions. Methods: This was a prospective, interventional, comparative, and observational study. A total of 80 eyes, consisting of 40 eyes without ocular comorbidities (group A) and 40 eyes with ocular comorbidities (group B) that were being treated with Nd: YAG capsulotomy for PCO, were included. Visual outcome and complications of Nd: YAG capsulotomy were studied. Results: The mean age of group A patients was 61.65 ± 8.85 years and that of group B patients was 63 ± 10.46 years. Of the total, 38 (47.5%) were men and 42 (52.5%) were women. In group B, the ocular comorbidities were moderate nonproliferative diabetic retinopathy (NPDR) (n = 14 eyes; 14/40 = 35%), subluxated intraocular lens (IOL; <2 clock hours of subluxation; n = 6), age?related macular degeneration (ARMD; n = 6), post?uveitic eyes (having old signs of uveitis, no episode of uveitis since the last 1 year; n = 5), and operated cases of traumatic cataract (n = 4). The mean energy required in groups A and B was 46.95 ± 25.92 and 42.62 ± 21.85 mJ, respectively (P = 0.422). The average energy requirement in Grade 2, Grade 3, and Grade 4 PCO was 22.30, 41.62, and 79.52 mJ, respectively. An increase in intraocular pressure (IOP) of >5 mmHg from pre?YAG levels was observed in one patient in each group on day 1 postprocedure, for which medical treatment was given to both patients for 7 days. One patient in each group had IOL pitting. No patient had any other complications attributable to ND:YAG capsulotomy. Conclusion: Nd:YAG laser posterior capsulotomy is a safe procedure for PCO in patients with comorbidities. Visual outcomes were excellent after Nd:YAG posterior capsulotomy. Although a transient increase in IOP was noted, the response to treatment was good and a long?term increase in IOP was not observed

Effect of aluminum-fluoride interactions on overall cognitive function of aluminum plant workers / 环境与职业医学

Background Aluminum and fluoride are neurotoxic, and aluminum exposure alone is closely related to the overall cognitive function of operational workers. It is unclear about the effect of aluminum and fluoride interactions on cognitive function. Objective To evaluate a potential interaction effect of blood aluminum and urinary fluoride on the overall cognitive function of workers working in an aluminum plant. Methods Using cluster sampling, 230 workers in the electrolysis workshop of an aluminum group company in Shanxi Province were selected, and plasma aluminum concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS) and urinary fluoride by ion-selective electrode. The study participants were divided into a low blood aluminum group and a high blood aluminum group according to the median (M) of blood aluminum concentration, and a low urinary fluoride group and a high urinary fluoride group by a predetermined cutoff point (2.160 mg·L−1). The Montreal Cognitive Assessment-Beijing (MoCA-BJ) was used to assess overall cognitive function of the workers. Logistic regression model was used to analyze the relationship between blood aluminum, urinary fluoride, and mild cognitive impairment (MCI), including multiplicative interaction analysis and correlation analysis; R language was used to fit an additive interaction model of blood aluminum and urinary fluoride on MCI and to calculate synergy index (S), relative excess risk due to interaction (RERI), and attributable proportion due to interaction (API). Results Among the 230 operational workers, the median blood aluminum concentration (P25, P75) was 40.11 (25.16, 58.89) µg·L−1, and there were 104 cases of abnormal urinary fluoride, with an abnormality rate of 45.2%. There was a multiplicative interaction (OR=7.783, 95%CI: 1.377, 43.991) and no additive interaction (RERI=0.030, 95%CI: −0.498, 0.559; API=0.018, 95%CI: −0.279, 0.316; S=1.049, 95%CI: 0.519, 2.118) for the effect between blood aluminum and urinary fluoride on overall cognitive function of the workers. The logistic regression analysis showed that the risk of MCI was 12.105 (95%CI: 2.802, 52.287) times higher in workers with both high blood aluminum and high urinary fluoride than in those with low blood aluminum and low urinary fluoride, after adjusting for selected influencing factors. Conclusion Occupational exposure related high blood aluminum and high urinary fluoride are risk factors for cognitive dysfunction, and the coexistence of both indicators increases the risk of MCI in workers with occupational aluminum exposure, with a multiplicative interaction.

Correlation between aluminum concentration and miR-134-3p expression in peripheral blood in occupational aluminum exposed workers / 环境与职业医学

Background Previous studies show that aluminum exposure could increase the expression of miRNA-134-3p, which is involved in the mechanism of aluminum induced learning and memory impairment. However, it has not been investigated whether the expression level of miRNA-134-3p in the peripheral blood of occupational aluminum exposed workers is related to the blood aluminum concentration yet. Objective To evaluate a potential correlation between aluminum concentration in peripheral blood and miR-134-3p expression in occupational aluminum exposed workers. Methods A total of 184 male aluminum workers in the electrolytic aluminum workshop, aluminum oxide workshop, and thermal power workshop of an aluminum plant in Shanxi were selected by cluster sampling. They were divided into four groups (Q1-Q4) according to the quartiles of blood aluminum concentration, with 46 workers in each group. The basic information of workers was collected by questionnaire survey, and the cognitive function of workers was evaluated by Montreal Cognitive Assessment (MoCA). The plasma of workers was collected, and the relative expression level of miR-134-3p in plasma was detected by real-time quantitative polymerase chain reaction (RT-PCR). The plasma aluminum concentration was detected by inductively coupled plasma mass spectrometry (ICP-MS). The associations among workers' peripheral blood aluminum concentration, plasma miR-134-3p expression level, and total MoCA score were evaluated by generalized linear models. Results The workers' medians (P25, P75) of blood aluminum concentration, plasma relative expression level of miR-134-3p, and MoCA score were 39.31 (25.30, 57.41) μg·L-1, 2.93 (2.29, 3.74), and 22.0 (20.0, 26.0), respectively. The results of the generalized linear model showed that after adjusting for age, body mass index, smoking, and alcohol consumption, compared with the Q1 group, blood aluminum in the Q2, Q3, or Q4 group had an impact on related plasma miR-134-3p expression level and total MoCA score (P<0.05). With increasing blood aluminum concentration, the expression level of miR-134-3p in workers' plasma gradually increased, showing a positive correlation (b>0, Ptrend<0.001), while the total score of MoCA gradually decreased, showing a negative correlation (b<0, Ptrend<0.001). As the expression level of miR-134-3p in plasma increased, the total score of MoCA gradually decreased, showing a negative correlation (b<0, Ptrend<0.001). There was a linear relationship between peripheral blood aluminum concentration and plasma relative expression level of miR-134-3p of the workers in the middle school and below group and the high school group (Ptrend<0.05), b (95%CI)=1.796 (1.248, 2.344) and 1.192 (0.874, 1.510), and no correlation was found in the workers in the college and above group (Ptrend>0.05). Conclusion Occupational aluminum exposure can lead to an increase in the expression level of miR-134-3p in plasma of workers, which may be related to a decrease in cognitive function of workers.

Sirt1-Keap1/Nrf2 signaling pathway mechanism of cognitive dysfunction induced by subchronic aluminum exposure in rats / 中国病理生理杂志

AIM:To investigate the effects of subchronic aluminum exposure on the expression of silent infor-mation regulator(Sirt1),Kelch-like ECH-associated protein 1(Keap1),nuclear factor E2-related factor 2(Nrf2),and microRNA-128-3p(miR-128-3p)in the hippocampus of rats.Additionally,we aimed to explore the mechanism of miR-128-3p and the Sirt1-Keap1/Nrf2 signaling pathways in aluminum-induced cognitive impairment in rats.METHODS:Thirty-two healthy 6-week-old SPF male SD rats,weighing(190±20)g,were randomly divided into four groups based on body weight:control group,low-dose(10 μmol/kg)group,medium-dose(20 μmol/kg)group,and high-dose(40 μmol/kg)group,with 8 rats in each group.The rat exposure model was established by intraperitoneal injection of maltol alumi-num.The Morris water maze test was used to assess the learning and memory ability of the rats.Western blot analysis was performed to measure the protein expression of Sirt1,Keap1 and Nrf2 in the hippocampus,while RT-qPCR was used to measure the expression of miR-128-3p in the hippocampus.The level of reactive oxygen species(ROS)in the cerebral cor-tex was detected using fluorescence staining in frozen sections.RESULTS:(1)In the positioning cruise experiment,the escape latency of the aluminum exposure group was significantly higher than that of the control group on the 3rd,4th,and 5th days(P＜0.05).On day 6,the number of times the rats crossed the platform and the platform quadrant in the high-dose group was reduced compared to the control and low-dose groups(P＜0.01).(2)The expression levels of Sirt1 and Nrf2 in the hippocampal tissues of all groups decreased gradually with increasing maltol aluminum exposure dose.The ex-pression level of Keap1 increased gradually with increasing maltol aluminum exposure dose.The expression level of miR-128-3p in the high-dose group was significantly higher than that in the control group(P＜0.05).(3)The content of gluta-thione peroxidase in the hippocampus of rats decreased with increasing exposure dose,while ROS levels gradually in-creased.CONCLUSION:Subchronic aluminum exposure can increase the expression of miR-128-3p in the rat hippo-campus and suppress the Sirt1-Keap1/Nrf2 signaling pathway.This inhibition prevents the activation of the Sirt1-Keap1/Nrf2 signaling pathway,leading to a reduced antioxidant capacity.The imbalance in the antioxidant system in rats results in oxidative damage to nerve cells and a subsequent decline in cognitive function.

Advances on mechanisms of regulated cell death in neurotoxicity of aluminum / 环境与职业医学

Aluminum is a light metal which is rich in the earth's crust and widely used. Recently, the adverse health effects of environmental and occupational aluminum exposure on human have attracted more and more attention. Aluminum exposure has toxic effects on the central nervous system and is believed to be closely related to the development and progression of Alzheimer's disease. The neurotoxic mechanism of aluminum is complex, especially the role of regulated cell death (RCD) in aluminum-induced neuronal death remains to be further studied. RCD refers to all modes of cell death regulated by multiple intracellular signal transduction pathways under physiological and pathological conditions, including apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis. This review summarized the morphological characteristics and mechanisms of each RCD mode in the process of aluminum-induced neuronal death, and discussed the relationship and transformation between different RCD modes, providing a new scientific basis for future studies on the treatment and intervention of neurotoxicity induced by aluminum exposure.

Absorption characteristics of aluminum hydroxide adjuvant with inactivated enterovirus 71 / 中国生物制品学杂志

@#Objective To explore the absorption characteristics of aluminum hydroxide adjuvant with inactivated enterovirus 71(EV71).Methods The morphology,purity and particle size distribution of inactivated EV71 particles were analyzed by transmission electron microscope,size exclusion chromatography HPLC(SEC-HPLC) and dynamic light scatter(DLS),and the morphology of aluminum hydroxide adjuvant nanoparticles was observed by transmission electron microscope.Using inactivated EV71 antigen content(4 000,6 000,8 000,10 000,11 000,12 000,13 000,14 000,20 000,30 000 U/mL),aluminum hydroxide adjuvant concentration [0.35,0.25,0.17,0.085 mg/mL(aluminum content)],adsorption time(0.30 and 120 min),ionic strength(sodium chloride concentration of 0.15,0.75 and 1.25 mol/L)and phosphorus-aluminum molar ratio(P/Al,0.15,0.64,2.08 and 7.87) as variables,the adsorption characteristics of aluminum hydroxide adjuvant with inactivated EV71 antigen were investigated.Results Inactivated EV71 particles mainly existed in the form of intact virus particles with a diameter of about 30 nm;Aluminum hydroxide adjuvant showed the characteristics of nanocrystallization,and the particle size was distributed within 200～700 nm.The inactivated EV71 antigen at the concentration of no more than 11 000 U/mL was completely absorbed by aluminum hydroxide adjuvant of 0.35 mg/mL(aluminum content),and no free antigen was detected in the supernatant;while from 12 000 U/mL,the content of free antigen in the supernatant increased with the increase of antigen content;the inactivated EV71 antigen of 250 U/mL was completely absorbed by various concentrations of aluminum hydroxide adjuvant,and no free antigen was detected in the supernatant;the adsorption effect of aluminum hydroxide adjuvant consistent after incubation for different time,and no free antigen was detected in the supernatant.Under the conditions of single dose of vaccine with aluminum hydroxide content(0.35 mg/mL) and inactivated EV71 antigen content(250 U/mL),sodium chloride ion strength had no effect on the adsorption of inactivated EV71 virus,while phosphate ion concentration significantly effected the adsorption.Conclusion Aluminum hydroxide adjuvant in a single dose of vaccine completely absorbed inactivated EV71 antigen,and group replacement played an important role.

Effect of aluminum exposure on abnormal phosphorylationof tau protein in PC12 cells of rats / 预防医学

Objective @#To investigate the effect of aluminum exposure on expression of miR-497-5p, wingless murine breast cancer virus integration site family member 3a (Wnt3a), β-catenin protein, glycogen synthase kinase-3β (GSK-3β) protein and tau protein in rat adrenal pheochromocytoma PC12 cells, so as to provide insight into unraveling the mechanisms underlying aluminum exposure-induced abnormal phosphorylation of tau protein.@* Methods@# PC12 cells were exposed to Al(mal)3 at concentrations of 0, 100, 200, 400 μmol/L for 24 h. The viability of PC12 cells was measured using cell counting kit-8 (CCK-8) assay. The relative expression of miR-497-5p and Wnt3a was detected using a real-time fluorescent quantitative PCR (RT-qPCR) assay, and the expression of Wnt3a, β-catenin, GSK-3β, P-GSK-3β (Ser9), tau and p-tau (Ser396) proteins were determined using Western blotting. @*Results @#The viability of PC12 cells appeared a tendency towards a decline with the increase of aluminum dose (Ftrend=323.473, P=0.001). RT-qPCR assay detected that the relative miR-497-5p expression appeared a tendency towards a rise with the increase of aluminum dose (Ftrend=14.888, P=0.031), and the relative Wnt3a expression appeared a tendency towards a decline with the increase of aluminum dose (Ftrend=165.934, P<0.001). The miR-497-5p expression negatively correlated with the relative Wnt3a expression (r=-0.693, P=0.012). The expression of Wnt3a (Ftrend=357.656, P=0.001), β-catenin (Ftrend=208.750, P=0.001) and p-GSK-3β (Ser9) proteins (Ftrend=512.583, P<0.001) appeared a tendency towards a decline with the increase of aluminum dose, and the expression of GSK-3β (Ftrend=39.965, P<0.001), tau (Ftrend=277.929, P=0.006) and p-tau (Ser396) proteins (Ftrend=96.247, P=0.002) appeared a tendency towards a rise with the increase of aluminum dose. @*Conclusion@# Up-regulation of miR-497-5p and GSK-3β expression and down-regulation of Wnt3a and β-catenin expression may be a mechanism underlying aluminum exposure-induced abnormal phosphorylation of tau protein.

Role of STAT3 activated NLRP3 inflammasomes in BV2 cell inflammatory response induced by maltol aluminum / 环境与职业医学

Background Aluminum activates signal transducer and activator of transcription 3 (STAT3), causing microglial nucleotide-binding and oligomerization domain-like receptors protein 3 (NLRP3) inflammasome activation and inflammatory responses and producing neurotoxicity. Objective To explore the role of STAT3 regulated NLRP3 inflammasomes in the inflammatory response of mouse microglia cell line (BV2) cells induced by maltol aluminum [Al(mal)3]. Methods BV2 cells were assigned to five groups: one control group, three Al(mal)3 exposure groups (low, medium, and high doses at 40, 80, and 160 μmol·L−1 Al(mal)3 respectively), and one C188-9 (STAT3 antagonist) intervention group [10 μmol·L−1 C188-9 +160 μmol·L−1 Al(mal)3]. Cell viability was detected by CCK8. The expression of M1/M2 type markers, i.e. CD68/CD206, STAT3, p-STAT3, NLRP3, cleaved-casepase-1, and apoptosis-associated speck-like protein (ASC) in BV2 cells were detected by Western blotting, and proinflammatory cytokines interleukin (IL)-1β and IL-18, and anti-inflammatory cytokine IL-10 were determined by ELISA. Results The results of cell viability assay showed that cell viability gradually decreased with the increase of Al(mal)3 dose. Compared with the control group, the cell viability of the Al(mal)3 high-dose group was decreased by 18% (P<0.05); compared with the Al(mal)3 high-dose group, the cell viability of the C188-9 intervention group was significantly elevated by 14% (P<0.05). Compared with the control group, the expression levels of CD68 in the Al(mal)3 low-, medium-, and high-dose groups were elevated by 19%, 20%, and 21%, respectively (P<0.05); the expression level of CD206 in the Al(mal)3 high-dose group was decreased by 25% (P<0.05). Compared with the Al(mal)3 high-dose group, the expression level of CD68 in the C188-9 intervention group was reduced by 9% (P<0.05), whereas the expression level of CD206 was elevated by 22% (P<0.05). Compared with the control group, the p-STAT3 protein expression and the p-STAT3/STAT3 ratio in the Al(mal)3 high-dose group increased by 129% and 127%, respectively (P<0.05). Compared with the Al(mal)3 high-dose group, the p-STAT3 protein expression and the p-STAT3/STAT3 ratio in the C188-9 intervention group were decreased by 55% and 54%, respectively (P>0.05). Compared with the control group, the expression level of NLRP3 protein increased by 75% in the Al(mal)3 high-dose group (P<0.05), the expression levels of cleaved-casepase-1 protein increased by 28% and 35% in the Al(mal)3 medium- and high-dose groups (P<0.05), and the expression levels of ASC increased by 22%, 25%, and 53% in the Al(mal)3 low-, medium- and high-dose groups (P<0.05), respectively. Compared with the Al(mal)3 high-dose group, the expression levels of NLRP3, cleaved-casepase-1, and ASC proteins in the C188-9 intervention group decreased by 30%, 19%, and 32%, respectively (P<0.05). Compared with the control group, the levels of IL-1β in the Al(mal)3 medium- and high-dose groups increased by 18% and 21%, respectively (P<0.05), and the level of IL-18 in the Al(mal)3 high-dose group increased by 10% (P<0.05). Compared with the Al(mal)3 high-dose group, the IL-18 levels were reduced by 23% in the C188-9 intervention group (P<0.05). The content of anti-inflammatory factor IL-10 did not differ significantly between groups (P>0.05). Conclusion Aluminum can induce inflammatory responses in BV2 microglia and is predominantly pro-inflammatory, and the mechanism may involve STAT3 regulation of NLRP3 inflammasome secretion of inflammatory factors.

Determination uncertainty of aluminum residues in human albumin using top-down evaluation / 中国输血杂志

【Objective】 To evaluate the determination uncertainty of aluminum residues in human albumin by inductively coupled plasma mass spectrometry (ICP-MS). 【Methods】 The aluminum residues in human albumin was determined by ICP-MS, and the top-down method was applied to assess the reasons of uncertainty and calculate the uncertainty. 【Results】 The relative standard uncertainty of the aluminum content in human albumin at the three quality control levels was 0.54 ng/mL, 1.68 ng/mL and 4.54 ng/mL, respectively, which met the requirements of the guidelines for bioanalytical methods in the Chinese Pharmacopoeia(2020). 【Conclusion】 The top-down method is simple and quick to assess the uncertainty of aluminum residues in human albumin, and is suitable for the uncertainty assessment of analytical methods in biological laboratories.

Optimization for condition of adsorbing hepatitis A virus antigen with aluminum hydroxide adjuvant and evaluation of immunogenicity of adsorption products / 中国生物制品学杂志

@#Objective To optimize the adsorption condition of hepatitis A virus(HAV)antigen by aluminum hydroxide[Al(OH)_3]adjuvant and evaluate the immunogenicity of the adsorbed products. Methods The final molar concentration of buffer(0. 01,0. 02 and 0. 04 mol/L),pH value(5. 5,6. 0,6. 5,7. 0,7. 5 and 8. 0),final molar concentration of sodium chloride(NaCl)(0. 075,0. 13,0. 15,0. 17,0. 45,0. 75 and 1. 0 mol/L),mixing mode(mixing after dilution and mixing directly without dilution)and dropping order[HAV stock solution into Al(OH)_3 solution,and Al(OH)_3 solution into HAV stock solution]were selected for single factor screening. Taking Al(OH)_3 adsorption rate as the evaluation index,the selected factors were optimized by orthogonal test. NIH mice were immunized intraperitoneally with adsorbed products prepared under optimal and suboptimal combination conditions with 0. 5 mL/mouse,10 mice in each group with half male and half female. After 28 d of immunization,the blood samples were collected from eyeball or heart,and the serum was separated. The HAV antibody level was detected by ELISA,and the immunogenicity of adsorbed products was evaluated by the seroconversion rate of mouse serum antibody. Results The results of single factor screening test showed that the final molar concentration of buffer,pH value and final molar concentration of NaCl had significant influence on the adsorption effect(F = 6. 582,14. 007 and 8. 612,respectively,each P < 0. 05),while the mixing mode and dropping order had no effect(t =-0. 696 and 1. 153,respectively,each P > 0. 05). The final molar concentration of buffer was 0. 01 and 0. 02 mol/L,the pH value was 5. 5 ～ 7. 0,and the final molar concentration of NaCl was 0. 13 ～ 0. 17 mol/L. The orthogonal test showed that the order of the influence on adsorption effect was the final molar concentration of buffer > pH value > NaCl final molar concentration. The optimal combination was pH 6. 3 + final molar concentration of buffer 0. 01 mol/L + NaCl molar final concentration 0. 15 mol/L,and the suboptimal combination was pH 5. 8 + final molar concentration of buffer 0. 02 mol/L +NaCl final molar concentration 0. 17 mol/L. The seroconversion rate of serum antibody in mice immunized with the adsorbed products prepared by the optimal and suboptimal combination was both 100%. Conclusion The adsorbed products prepared under the optimized conditions have good immunogenicity,which lays a foundation of the research of inactivated hepatitis A vaccine

Mediating role of brain functional connectivity in cognitive decline induced by occupational aluminum exposure in workers / 环境与职业医学

Background Occupational aluminum exposure may associate with cognitive impairment in workers. At present, brain functional imaging data are not available for evaluating cognitive dysfunction in workers with occupational exposure to aluminum. The role of brain functional connectivity in cognitive decline associated with occupational aluminum exposure is not clear yet. Objective To explore potential mediating effect of brain functional connectivity value on cognitive decline induced by occupational aluminum exposure, to assess the relationship between cognitive impairment and brain functional connectivity, and to identify appropriate imaging evidence of early cognitive changes induced by occupational aluminum exposure. Methods This study used a subset data from a previous cross-sectional survey. Based on the data of aluminum-exposed workers, over 40 years old, aluminum-exposed working years >1 year, Montreal International Cognitive Assessment (MoCA) (Beijing version) score <26 points, 20 workers were selected as the case group, and 40 healthy workers with the same basic conditions (age, smoking, drinking, etc.) in non-aluminum production were selected as the control group with a 1∶2 matching ratio. The basic information of the subjects was collected, plasma aluminum level and cognitive function level were evaluated, and different brain functional connectivity values of default mode network (DMN) were measured by magnetic resonance imaging. The mediating effect analysis was conducted to examine the role of brain functional connectivity in the relationship between aluminum exposure and cognitive function. Results The plasma aluminum concentration of the case group was 1.76 times higher than that of the control group [(33.04±12.02) µg·L−1 vs (18.74±8.95) µg·L−1, P<0.05]; the MoCA score was 9.5 points lower [(18.35±2.64) vs (27.85±0.92), P<0.05]. The mean functional connection values of DMN1 and DMN2 in the case group were lower than those in the control group (P<0.05). The mean functional connection values of the left precuneus, left middle cingulate cortex, left superior medial gyrus, left precentral gyrus, and left cerebellum also decreased in the case group compared with the control group (P<0.05). Plasma aluminum concentration was negatively correlated with DMN1 functional connectivity value and MoCA scores (b=−0.004, 95%CI: −0.008–−0.001; b=−0.15, 95%CI: −0.233–−0.067; P<0.05). The mean functional connection values of DMN1 and DMN2 were positively correlated with MoCA scores (b=10.945, 95%CI: 5.574–16.316; b=10.107, 95%CI: 2.457–17.758; P<0.05). With the increase of plasma aluminum concentration, MoCA score decreased, but when the plasma aluminum concentration exceeded 19.50 µg·L−1, MoCA score decreased slowly. With the increase of the mean functional connectivity value of DMN1, MoCA score increased, but when the mean functional connectivity value of DMN1 exceeded 1.05 and continued to increase, the increase of MoCA score slowed down. The results of mediating effect analysis showed that the functional connectivity value of DMN1 partially mediated the relationship between plasma aluminum concentration and MoCA score, and the mediating effect was 25.80%. Conclusion Cognitive impairment in occupational aluminum-exposed workers is closely related to brain resting-state functional connectivity. There is a dose-response relationship of plasma aluminum concentration with DMN1 functional connectivity value and MoCA scores, and DMN1 functional connectivity value partially mediates the relationship between plasma aluminum concentration and MoCA scores. The brain functional connectivity value can be used as meaningful imaging data to study the cognitive decline induced by chronic aluminum exposure.

Role of TLR2/NF-κB signaling pathway in aluminum-induced inflammatory response in GMI-R1 cells / 中国职业医学

{L-End}Objective To investigate the role and mechanism of Toll-like receptor 2 (TLR2)/nuclear factor-κB(NF-κB) signaling pathway in the inflammatory response induced by aluminum in the rat GMI-R1 microglia cells. {L-End}Methods GMI-R1 cells in logarithmic growth phase were randomly divided into the control group, positive control group, and low-, medium-, and high-dose groups. The cells in the three dose groups were stimulated with maltolol aluminum at concentrations of 100, 200, and 400 μmol/L, respectively. The cells in the positive control group were stimulated with lipopolysaccharide at a mass concentration of 20 mg/L, while the cells in the control group were not treated. The morphological changes of cells were observed, and the cell survival rate was evaluated by CCK-8 method after 24 hours of culture. The secretion levels of tumor necrosis factor-α (TNF-α), interleukin (IL) -12 and IL-4 were detected by enzyme-linked immunosorbent assay. The relative protein expression of TLR2, NF-κB P65, cluster of differentiation (CD) 68 and CD206 of cells was detected by Western blotting, and the expression of CD68 and CD206 of cells was detected by immunofluorescence method. {L-End}Results The results of cell morphology showed that the number of GMI-R1 cells decreased, the number of activated cells increased, the degree of cell cytoplasm filling decreased, and the cell protrusions elongated with the increase of exposure dose, showing a dose-response relationship. The cell viability of the positive control group and the medium- and high-dose groups were significantly lower than those of the control group (all P<0.05). The secretion levels of TNF-α, IL-12 and the relative expression of TLR2 and CD68 proteins increased (all P<0.05) while the secretion level of IL-4 decreased (all P<0.05) in the cells of positive control group compared with the control group. The secretion levels of TNF-α and IL-12 increased (all P<0.05) while the secretion levels of IL-4 decreased in the cells of the three doses groups (all P<0.05), compared with the control group, and all showed a dose-effect relationship. The relative expression of TLR2 protein in the cells of the three doses groups increased (all P<0.05) compared with the control group. The relative expression of NF-κB p65 and CD68 protein in the cells of the medium- and high-dose groups increased (all P<0.05), but the relative expression of CD206 protein decreased (all P<0.05) compared with the control group. The relative expression of TLR2 and NF-κB p65 protein increased (all P<0.05) while the relative expression of CD206 protein decreased (all P<0.05) in cells of the high-dose group, compared with the low- and medium-dose groups. The average fluorescence intensity of CD68 increased (all P<0.05) while the average fluorescence intensity of CD206 decreased in the cells of high-dose group and the positive control group (all P<0.05), compared with the control group. {L-End}Conclusion Aluminum participated in and promoted the inflammatory response of GMI-R1 cells through the TLR2/NF-κB signaling pathway.

Effect of miR-96-5p targeting IRS1 on apoptosis of PC12 cells induced by aluminum maltol / 中华劳动卫生职业病杂志

Objective: To investigate the effect and mechanism of miR-96-5p on apoptosis of PC12 cells induced by maltol aluminum. Methods: In January 2021, PC12 cells at logarithmic growth phase were divided into blank control group and low, medium and high dose group. Cells in each group were treated with 0, 100, 200 and 400 μmol/L maltol aluminum for 24 hours respectively. Cells were collected and cell apoptosis rates were detected by flow cytometry, miR-96-5p and insulin receptor substrate 1 (IRS1) mRNA expressions were detected by qRT-PCR, and the protein expression levels of cysteine protease 3 (Caspase3) 、activated cysteine protease 3 (Cleaved-caspase3) 、IRS1、phosphorylated protein kinase B (p-AKT) and phosphorylated glucose synthesis kinase 3β (p-GSK3β) were detected by western blotting. The target binding relationship between miR-96-5p and IRS1 was detected by double luciferase reporter gene experiment. The miR-96-5p inhibitor cells and negative control cells were constructed after transfecting PC12 cells with miR-96-5p inhibitor for 24 hours. The cells were divided into blank control group, negative control group, aluminum exposure group, aluminum exposure+negative control group, aluminum exposure+miR-96-5p inhibition group, and miR-96-5p inhibition group. After transfecting PC12 cells with miR-96-5p inhibition and IRS1 siRNA for 24 h, the cells were divided into aluminum exposure+miR-96-5p inhibition+negative control group and aluminum exposure+miR-96-5p inhibition+IRS1 inhibition group. The control group was cultured in complete culture medium, and cells in the aluminum exposure group were treated with 200 μmol/L maltol aluminum for 24 hours. Cells in each group were collected and the apoptosis rate, miR-96-5p and IRS1 mRNA expression levels, as well as protein expression levels of Caspase3, Cleaved-caspase3, IRS1, p-AKT, and p-GSK3β were measured. Results: After 24 hours of exposure, compared with blank control group and low-dose group, the apoptosis rates, relative expressions of Caspase3 and Cleaved-caspase3 proteins, and relative expressions of miR-96-5p in the medium and high-dose groups of PC12 cells were significantly increased, while the relative expression levels of IRS1 mRNA, IRS1, p-AKT and p-GSK3β proteins were significantly decreased (P<0.05). Targetscan prediction and double luciferase report experiment both proved that IRS1 was a direct target gene of miR-96-5p. In the transfection experiment, compared with the aluminum exposure group, the apoptosis rate, the relative expressions of Caspase3 and Cleaved-caspase3 proteins, the relative expression of miR-96-5p in the aluminum exposure+miR-96-5p inhibition group were significantly decreased, while the relative expression levels of IRS1 mRNA and IRS1, p-AKT and p-GSK3β proteins were significantly increased (P<0.05). In the IRS1 low expression experiment, compared with the aluminum exposure+miR-96-5p inhibition+negative control group, the apoptosis rate, the relative expressions of Caspase3 and Cleaved-caspase3 proteins in the aluminum exposure+miR-96-5p inhibition+IRS1 inhibition group were significantly increased, while the relative expression levels of IRS1 mRNA and IRS1, p-AKT and p-GSK3β proteins were significantly decreased (P<0.05) . Conclusion: The increased expression of miR-96-5p and the targeted inhibition of IRS1 may be one of the mechanisms of apoptosis of PC12 cells induced by maltol aluminum exposure.

Effect of Neodymium-Doped Yttrium Aluminum Garnet Laser Combined With Desensitizing Toothpaste on Dentinal Tubule Occlusion Against Acid Challenge / 中国医学科学院学报

Objective To assess the effects of different application sequences of neodymium-doped yttrium aluminum garnet(Nd∶YAG)laser and the desensitizing toothpaste containing stannous fluoride on dentinal tubule occlusion.Methods Twelve intact third molars freshly extracted from human were selected and prepared into dentin slices with a thickness of 0.8 mm.Each dentin slice was subdivided into four small slices,three of which were etched with 6% citric acid and randomly assigned to the following three groups(n=12):(1)control group:no treatment;(2)Nd∶YAG+toothbrushing(TB)group:first irradiated with Nd∶YAG laser and then brushed with desensitizing toothpaste;(3)TB+Nd∶YAG group:first brushed with desensitizing toothpaste and then irradiated with Nd∶YAG laser.The Nd∶YAG laser irradiation were carried out at 1 W,15 pulses/s,and the pulse width of 150 μs for 10 s(for a total of 6 cycles).After the above treatment,the 12 dentin slices from the Nd∶YAG+TB and TB+Nd∶YAG groups were randomly assigned to four subgroups(n=3)and subjected to acid etching in the Coca-Cola solution for 0,5,10,and 15 min.A scanning electron microscope was used to observe and photograph the dentin slices in each group,and eight single-blinded examiners scored the slices according to uniform criteria.The analysis of variance was carried out to compared the scores between groups.Results Before acid etching,the dentin tubule occlusion scores of the Nd∶YAG+TB and TB+Nd∶YAG groups were(4.83±0.09) scores and(3.85±0.66) scores,respectively,which had no significant difference between each other(P=0.0590)and were higher than that[(0.10±0.07)scores]of the control group(both P<0.0001).The dentin tubule occlusion scores of the Nd∶YAG+TB group after acid etching for 5,10,and 15 min were(4.33±0.60)scores,(4.27±0.24)scores,and(3.63±0.07)scores,respectively,which were not significantly different from those[(4.04±0.10)scores,(3.76±0.59)scores,and(3.17±0.29)scores,respectively]of the TB+Nd∶YAG group(all P>0.05).In the Nd∶YAG+TB subgroup,the dentin tubule occlusion score after acid etching for 15 min was significantly lower than that before acid etching(P=0.0011).In the TB+Nd∶YAG group,there was no statistically significant difference in the score between before and after acid etching(P>0.05).Conclusions Nd∶YAG laser irradiation with appropriate parameters combined with the use of desensitizing toothpaste could produce an excellent occluding effect on dentinal tubules regardless of the sequence.However,brushing with desensitizing toothpaste followed by Nd∶YAG laser irradiation produced more consistent dentin sealing after acid etching.

Woody species distribution across a savanna-dry forest soil gradient in the Brazilian Cerrado / Distribuição de espécies arbóreas em gradiente de solo savana-floresta seca no Cerrado brasileiro

Abstract Although richness and distribution of woody species in the Cerrado physiognomies have been extensively studied, the shifts of woody species from savanna physiognomies to dry forests have not yet been addressed. Here, we investigate the effect of soil physical-chemical traits on the woody species turnover between adjacent cerrado stricto sensu and dry forest physiognomies. Woody species were surveyed, and soil and topographic variables measured, in 30 10×40 m plots systematically distributed, with 15 plots in each physiognomy. We found a spatially structured distribution of woody species, and differences of soil traits between cerrado stricto sensu and dry forest areas, mainly related to the aluminum saturation, base saturation, and available phosphorus. Aluminum saturation increased toward the savanna area, while base saturation increased toward the dry forest. Most woody species predominated in one physiognomy, such as Callisthene major in the cerrado stricto sensu and Anadenanthera colubrina in the dry forest. Only 20% of the species were widely distributed across both physiognomies or, not often, restricted to the intermediary values of the soil gradient. General results indicate that contrasting soil traits between cerrado stricto sensu and dry forest produce a strongly spatially organized and sharp transition in terms of species distribution between these physiognomies.

Resumo Embora a distribuição e a riqueza em espécies arbóreas nas fitofisionomias do Cerrado venham sendo bastante estudadas, a transição entre savanas e florestas deciduais ainda não foi abordada. Investigamos o efeito de características físico-químicas do solo sobre a distribuição de espécies arbóreas em região de contato entre cerrado sentido restrito e floresta estacional decidual (FED). As espécies arbóreas foram amostradas sistematicamente, e variáveis de topografia e características do solo foram medidas em 30 parcelas de 10×40 m, sendo 15 parcelas em cada fisionomia. A distribuição das espécies arbóreas foi espacialmente estruturada, e as características do solo diferiram entre as áreas de cerrado sentido restrito e FED, principalmente relacionadas à saturação de alumínio, saturação de bases e teores de fósforo. A saturação de alumínio aumentou em direção ao cerrado sentido restrito, enquanto a saturação de bases aumentou em direção à FED. A maioria das espécies arbóreas predominou em uma das fisionomias, como Callisthene major em cerrado sentido restrito e Anadenanthera colubrina em FED. Apenas 20% das espécies foram amplamente distribuídas em ambas as fisionomias ou, em poucos casos, restritas aos valores intermediários do gradiente de solo. Os resultados indicam um forte contraste de características do solo entre o cerrado sentido restrito e a FED, assim como uma transição acentuada e espacialmente organizada quanto à distribuição de espécies arbóreas.

Woody species distribution across a savanna-dry forest soil gradient in the Brazilian Cerrado / Distribuição de espécies arbóreas em gradiente de solo savana-floresta seca no Cerrado brasileiro

Although richness and distribution of woody species in the Cerrado physiognomies have been extensively studied, the shifts of woody species from savanna physiognomies to dry forests have not yet been addressed. Here, we investigate the effect of soil physical-chemical traits on the woody species turnover between adjacent cerrado stricto sensu and dry forest physiognomies. Woody species were surveyed, and soil and topographic variables measured, in 30 10×40 m plots systematically distributed, with 15 plots in each physiognomy. We found a spatially structured distribution of woody species, and differences of soil traits between cerrado stricto sensu and dry forest areas, mainly related to the aluminum saturation, base saturation, and available phosphorus. Aluminum saturation increased toward the savanna area, while base saturation increased toward the dry forest. Most woody species predominated in one physiognomy, such as Callisthene major in the cerrado stricto sensu and Anadenanthera colubrina in the dry forest. Only 20% of the species were widely distributed across both physiognomies or, not often, restricted to the intermediary values of the soil gradient. General results indicate that contrasting soil traits between cerrado stricto sensu and dry forest produce a strongly spatially organized and sharp transition in terms of species distribution between these physiognomies.

Embora a distribuição e a riqueza em espécies arbóreas nas fitofisionomias do Cerrado venham sendo bastante estudadas, a transição entre savanas e florestas deciduais ainda não foi abordada. Investigamos o efeito de características físico-químicas do solo sobre a distribuição de espécies arbóreas em região de contato entre cerrado sentido restrito e floresta estacional decidual (FED). As espécies arbóreas foram amostradas sistematicamente, e variáveis de topografia e características do solo foram medidas em 30 parcelas de 10×40 m, sendo 15 parcelas em cada fisionomia. A distribuição das espécies arbóreas foi espacialmente estruturada, e as características do solo diferiram entre as áreas de cerrado sentido restrito e FED, principalmente relacionadas à saturação de alumínio, saturação de bases e teores de fósforo. A saturação de alumínio aumentou em direção ao cerrado sentido restrito, enquanto a saturação de bases aumentou em direção à FED. A maioria das espécies arbóreas predominou em uma das fisionomias, como Callisthene major em cerrado sentido restrito e Anadenanthera colubrina em FED. Apenas 20% das espécies foram amplamente distribuídas em ambas as fisionomias ou, em poucos casos, restritas aos valores intermediários do gradiente de solo. Os resultados indicam um forte contraste de características do solo entre o cerrado sentido restrito e a FED, assim como uma transição acentuada e espacialmente organizada quanto à distribuição de espécies arbóreas.